Nefopam is the active ingredient of Acupan®. It is a non-opioid centrally acting antalgic of the benzoxazocine family (Klohs et al. (1972) Arzneimittelforschung 22:132-3). Its advantages include, in particular, the absence of respiratory depressant effects. Its mode of action is still not properly understood but seems to require monoamine uptake inhibition, which distinguishes it from paracetamol and non-steroidal anti-inflammatories (NSAIDs). NSAIDs are more or less selective inhibitors of the cyclooxygenase isoform 2 (COX-2) which thus have the effect of reducing the synthesis of prostaglandins in the central and peripheral nervous systems.

Currently, nefopam is principally used for the treatment of post-operative pain. In France, it is thus administered to approximately 20% of patients who have undergone surgical intervention (Fletcher et al. (2008) Pain 137:441-51). However, its own analgesic efficacy is sometimes not sufficient in painful surgeries and it is in fact often used in combination with other analgesics, in particular morphine, paracetamol and ketoprofen (NSAID) (Fletcher et al. (2008) Pain 137:441-51). However, those combinations have certain limitations.
Thus, although it permits a notable reduction in the amount of morphine administered for the same analgesic efficacy, the nefopam-morphine combination does not always enable the doses of morphine to be reduced sufficiently to eliminate the undesirable symptoms associated with its use (Du Manoir et al. (2003) Br. J. Anaesth. 91:836-841). The effect of the nefopam-ketoprofen combination has for its part been evaluated post-operatively as being synergistic, but only after moderately painful surgeries (Delage et al. (2005) Anesthesiology 102:12111216). In addition, the use of ketoprofen is often limited in time owing to its poor digestive tolerance.
It therefore remains to find a combination which makes it possible to benefit from the advantages of nefopam while at the same time offering some comfort of use for the patient.
Therefore, the analgesic efficacy of a combination of nefopam and diclofenac, another NSAID, has also been evaluated without any benefit being demonstrated compared with the use of diclofenac alone (Moffat et al. (1990) Anesthesia 45:302-305).
Ibuprofen is also a NSAID which brings about analgesia which is efficacious but less so than that of ketoprofen (Mills et al. (1973) British Medical Journal 4:82-84). Currently, ibuprofen is hardly ever used in the management of post-operative pain (Fletcher et al. (2008) Pain 137:441-51).
